Gangrene

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Edzel Lorraine Co, D.M.D., M.D.

Gangrene is a medical condition that involves necrosis and ischemia of a body tissue, mostly occurring in the digits or extremities. It usually appears as a black discoloration and sloughing of tissues. There are three main types of gangrene, namely wet gangrene, dry gangrene, and gas gangrene.

Gangrene originated from a Greek word that meant mortification of a human body part. It was first used as a noun in the British Isles during the 16th century. Surgeons most often used it to refer to the cure of external human conditions.

There are three main types of gangrene which include wet, dry, and gas gangrene. Sometimes it can be classified according to its site.

There are three types of gangrene and they have different pathophysiology. A reduced arterial perfusion is observed in dry gangrene which results in the compensatory arteriolar dilation, which eventually results in distal edema, and damage of the endothelial tissue. Saprogenic microorganisms such as Clostridium perfringens and Bacillus fusiformis are the most common organisms observed in wet gangrene which are responsible for infecting the tissues, thereby producing a putrid smell and edema. Group A Steptococcus and exotoxins from Clostridium perfringens are responsible for the local and systemic infection found in gas gangrene.

According to Hippocratic physicians, gangrene is brought about by three reasons. These include wound constriction that is followed by hemorrhage, body part compression, and necrosis due to bandages.

Gangrene can have several mimicking conditions despite the unique presence of necrotic tissue.

Ischemic or dry gangrene is commonly associated with peripheral artery disease (PAD). The most advanced stage of PAD is critical limb ischemia/ chronic limb-threatening ischemia, and it has an incidence rate of 1% in the United States. Gas gangrene is a rare condition, with an annual record of 1000 cases in the United States, 50% of which are due to traumatic injuries, 30% due to post-operative complications, and the remaining part is attributed to infections.

There are several risk factors for gangrene and these include penetrating trauma, blunt trauma, recent surgery, obesity, alcoholism, mucosal breach, skin breach, and immunosuppression.

Amputation and death are the most common consequence of critical limb ischemia/ chronic limb-threatening ischemia. Gas gangrene has higher fatality rate, ranging from 25% to 100%, if treatment is inadequate or delayed. Increased age, several comorbidities present, and involvement of trunk lead to a poor prognosis.

Chronic limb pain is the usual chief complaint of patients who developed gangrene.

Patients with gangrene may have varying presentations depending on the type of gangrene they have.

Evaluation of patients with ischemic gangrene is more focused on targeting the risk factors which include hyperlipidemia, diabetes, and renal failure. Laboratory tests to deal with these risk factors are usually requested for ischemic gangrene. Wet gangrene and gas gangrene are assessed with the help of cultures.

X-rays are utilized in the evaluation of gas gangrene to identify any present subcutaneous gas.

Computed tomography (CT scan) with contrast is the best initial imaging test for gangrene.

Magnetic resonance imaging (MRI) is not so useful in the evaluation of gas gangrene. The presence of gas is not very well detected using this imaging modality.

Other recommended imaging tests to consider in the evaluation of gangrene include ultrasound, duplex ultrasound, computed tomography / (CT) angiography, digital subtraction angiography, and magnetic resonance angiography / (MRA).

There are some useful tools that were developed to assess the possibility of gangrene. These include the recent development of the Society of Vascular Surgery which is called WIfI which stands for wound, ischemia, foot infection, and the Laboratory Risk Indicator for Necrotizing Fasciitis (LRINEC) score.

Ischemic gangrene can be medically treated with angiotensin-converting enzyme (ACE) inhibitors, beta-blockers, and antiplatelet drugs such as aspirin and clopidogrel. Wet gangrene and gas gangrene are treated with antibiotics which should cover microorganisms detected in culture of the specimen with gangrene.

The goal of surgical treatment in gangrene is to achieve revascularization to alleviate pain and avoid limb loss.

Gas gangrene can be prevented by always monitoring the blood glucose levels and maintaining them within the normal range, and regular foot inspection, most especially in those patients with diabetes. Post-exposure prophylaxis may be needed by immunocompromised individuals if they were in close contact with patients with necrotizing infection due to Group A streptococcus. Droplet and contact precautions are warranted to these susceptible individuals.

Early diagnosis and prompt medical and surgical treatment of gangrene are needed to prevent the rapid progression and worsening of the disease.

Gangrene is a potential life-threatening condition if not given prompt treatment. Although the incidence is just low, gangrene can generate a high healthcare cost.

A novel gene therapeutic approach is currently conducted to promote reperfusion and angiogenesis of ischemic tissues, which can help in limb salvage. Ongoing study on this approach is conducted on mice and it involves the intramuscular injection of adeno-associated virus/ (AAV) vector, and E-selectin.

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] Associate Editor(s)-in-Chief: Edzel Lorraine Co, D.M.D., M.D.

Gangrene originated from a Greek word “sphacelus” that meant mortification of a human body part.^[1][2] It was first used as a noun in the British Isles during the 16th century. Surgeons most often used it to refer to the cure of external human conditions. ^[2]

• Gangrene originated from a Greek word “sphacelus” that meant mortification of a human body part. ^[1][2]
• It was first used as a noun in the British Isles during the 16th century. ^[2]
• Surgeons most often used it to refer to the cure of external human conditions. ^[2]
• In the 17th century, this word was passed on from one person to another, until a metaphorical meaning was given by Shakespeare in Coriolanus:

                               "The service of the foote
                                Being once gangren'd, is not then respected
                                For what it was before." [2]

• Pathology became a new profession in the 19th century, and has made gangrene as a taxonomical umbrella with a myriad of species flourished.
• In 1915, gangrene was described by surgeon D’Arcy Power in his book Wounds of War:

 The wound generally becomes more or less emphysematous and discharges a thin brownish, offensive fluid, which contains bubbles of gas...
    The ineffective process continues after death and the swelling may rapidly become so great as to make the corpse unrecognizable.

• Table 1 lists the famous people who had contracted gangrene.

Table 1.Personalities With Significant Historical Contribution to the Discovery of Gangrene.

Name	Image	Description
Jean Baptiste Lully		French Baroque composer who had gangrene in January 1687. While performing in his Te Deum, he stabbed his toe with a pointed material, which caused the spread of infection in his leg. He refused amputation of his leg.
French King Louis XIV		He died due to gangrene on September 1, 1715.
Sebald Justinus Brugmans		A professor at Leyden University, Brugsman became the lead expert against hospital–gangrene. In 1814, he made a treatise on gangrene, and later on established the contagious property of this disease.
John M. Trombold		He was a surgeon during the American Civil War. He studied hospital gangrene and was able to come up with a revolutionary treatment for this (debridement and the use of intravenous and topical bromide solutions on infected wounds.
Father Camille Bulcke		He died on August 17, 1982 due to gangrene.

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] ; Associate Editor(s)-in-Chief: Edzel Lorraine Co, D.M.D., M.D.

There are three types of gangrene and they have different pathophysiology. A reduced arterial perfusion is observed in dry gangrene which results in the compensatory arteriolar dilation , which eventually results in distal edema, and damage of the endothelial tissue. ^[1] Saprogenic microorganisms such as Clostridium perfringens and Bacillus fusiformis are the most common organisms observed in wet gangrene which are responsible for infecting the tissues, thereby producing a putrid smell and edema. ^[2] Group A Steptococcus and exotoxins from Clostridium perfringens are responsible for the local and systemic infection found in gas gangrene.^[3]

There are three types of gangrene and they have different pathophysiology.

• A reduced arterial perfusion is observed in dry gangrene which results in the compensatory arteriolar dilation, which eventually results in distal edema, and damage of the endothelial tissue. ^[1]
• It is a type of coagulative necrosis which occurs in ischemic tissue. Closing </ref> missing for <ref> tag

• Saprogenic microorganisms such as Clostridium perfringens and Bacillus fusiformis are the most common organisms observed in wet gangrene. They are responsible for infecting the tissues, thereby producing a putrid smell and edema. ^[2]
• The pooling and accumulation of blood in the affected tissue promotes proliferation of bacteria.
• An edematous, putrid, soft, and dark tissue is observed.^[2]

• Group A Steptococcus and exotoxins from Clostridium perfringens are responsible for the local and systemic infection found in gas gangrene. ^[3]
• Clostridium perfringens produces a Clostridium– lecithinase called Alpha-toxin that contributes to tissue necrosis and systemic hemolysis.^[4][5]
• Rapid progression to shock is usually observed.

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1], Associate Editor(s)-in-Chief: Edzel Lorraine Co, D.M.D., M.D.

Gangrene can have several mimicking conditions despite the unique presence of necrotic tissue.

• Gangrene can have several mimicking conditions despite the unique presence of necrotic tissue.
• Table 1 outlines the various differential diagnosis for gangrene.

Table 1. Differential Diagnosis of Gangrene. ^[1]

Differential Diagnosis	Similar to:
Frostbite	Ischemia
Ergotism	Ischemia
Compartment syndrome	Ischemia
Calciphylaxis	Ischemia
Group A streptococcus infections	Gas gangrene
Septic shock	Gas gangrene
Toxic shock syndrome	Gas gangrene

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1], Associate Editor(s)-in-Chief: Edzel Lorraine Co, D.M.D., M.D.

Ischemic or dry gangrene is commonly associated with peripheral artery disease (PAD). The most advanced stage of PAD is critical limb ischemia/ chronic limb-threatening ischemia, and it has an incidence rate of 1% in the United States. Gas gangrene is a rare condition, with an annual record of 1000 cases in the United States, 50% of which are due to traumatic injuries, 30% due to post-operative complications, and the remaining part is attributed to infections. ^[1]

• Ischemic or dry gangrene is commonly associated with peripheral artery disease (PAD).
• The most advanced stage of PAD is critical limb ischemia/ chronic limb-threatening ischemia, and it has an incidence rate of 1% in the United States. ^[1]
• Periperhal artery disease of the lower extremities has a prevalence rate of 200 million, with up to 10% of them have critical limb ischemia/ chronic limb-threatening ischemia. ^[1]
• If an asymptomatic PAD is left untreated, progression to critical limb ischemia/ chronic limb-threatening ischemia in five years. ^[1]
• Gas gangrene is a rare condition, with an annual record of 1000 cases in the United States, 50% of which are due to traumatic injuries, 30% due to post-operative complications, and the remaining part is attributed to infections. ^[1]

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1], Associate Editor(s)-in-Chief: Edzel Lorraine Co, D.M.D., M.D.

There are several risk factors for gangrene and these include penetrating trauma, blunt trauma, recent surgery, obesity, alcoholism, mucosal breach, skin breach, and immunosuppression. ^{[1] [2] [3][4] [5] [6] [7] [8]}

There are several risk factors for gangrene and these include:

• Penetrating trauma
• Blunt trauma
• Minor laceration
• Recent surgery (urologic, colonic or gynecologic procedures).
• Obesity
• Alcoholism
• Mucosal breach (rectal fissures, hemorrhoids, episiotomy)
• Skin breach (insect bite, varicella lesion, injection drug use)
• Immunosuppression (cirrhosis, diabetes mellitus, HIV, etc.) ^{[1] [2]}

^{[3][4] [5] [6] [7] [8]}

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Edzel Lorraine Co, D.M.D., M.D.

Amputation and death are the most common consequence of critical limb ischemia/ chronic limb-threatening ischemia. ^[1] Gas gangrene has a higher fatality rate, ranging from 25% to 100%, if treatment is inadequate or delayed. Increased age, several comorbidities present, and involvement of trunk lead to a poor prognosis. ^[2]

• Amputation and death are the most common consequence of critical limb ischemia/ chronic limb-threatening ischemia. ^[1]
• Below-the-knee amputations lead to a higher ambulatory rate than above-the-knee amputations.^[3]

• There is a possibility of recurrence of critical limb ischemia/ chronic limb-threatening ischemia.
• Follow-up after revascularization procedures is needed for at least two years.^[4]
• Gas gangrene has higher fatality rate, ranging from 25% to 100%, if treatment is inadequate or delayed.
• Increased age, several comorbidities present, and involvement of trunk lead to a poor prognosis. ^[2]